PTH has multiple, powerful effects on bone but it's anabolic actions are poorly understood. In animals, intermittent PTH administration increases both cortical and trabexular bone mass and can prevent, or even reverse, bone loss. In elderly people with osteoporosis, intermittent PTH administration increases trabecular bone mass but may accelerate cortical bone loss. In young women made acutely estrogen deficient, PTH increases bone mineral density (BMD) in trabecular-rich sites with no clear effect on cortical bone. In this proposal we will examine the effects of long-term, intermittent PTH administration on bone mass and bone turnover in early menopausal women with normal BMD. We will evaluate the effects of PTH on both cortical and trabecular BMD, assess the importance of aging and/or prior bone loss on the skeletal response to PTH, and attempt to identify markers that perdict the skeletal response to PTH, and attempt to identify markers that perdict the skeletal response to PTH and may suggest underlying mechanisms. Our model of early monopausal women with osteoporosis so that studies of PTH in this group are more likely to have detecable and interpretable results. Furthermore, this model eliminates prior bone loss as a factor in the skelatal response to PTH. Effects of longterm, intermitent PTH administration on bone mineral density in early menopausal women with normal bone mass. The first specific aim will test the hypothesis that intermittent PTH administration prevents both cortical and trabecular bone loss (or even auguments bone mass) during the early phases of the natural menopause. The role of skeletal aging, and prior bone loss, in the responsiveness to interittent PTH. The second specific aim will test the hypothesis that aging, and/or prior bone loss, is an important determinant of the response to internittent PTH. Characterization of factors that predict the skeletal responiveness to longterm intermittent PTH administration. The third specific aim will attempt to identify biochemical markers that are associated with the skeletal response to long-term PTH administration. Considerable variability exists in the skeletal response of people to intermittent PTH administration.